David H Jang1, Clinton J Orloski1, Shawn Owiredu1, Frances S Shofer1, John C Greenwood1,2, David M Eckmann2,3. 1. Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
OBJECTIVE: Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis. DESIGN: Prospective observational study. SETTING: Single site tertiary academic emergency department. SUBJECTS: We enrolled a total of 48 subjects in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls. INTERVENTIONS: Peripheral blood mononuclear cells were measured with high-resolution respirometry (OROBOROS O2K). MEASUREMENTS AND MAIN RESULTS: The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 29 years old, respectively. In the Sepsis group, the median 1st 24-h SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared with 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared with the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared with the other group. There were no age-related differences in respiration between the Older and Younger control group. CONCLUSIONS: Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.
OBJECTIVE:Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis. DESIGN: Prospective observational study. SETTING: Single site tertiary academic emergency department. SUBJECTS: We enrolled a total of 48 subjects in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls. INTERVENTIONS: Peripheral blood mononuclear cells were measured with high-resolution respirometry (OROBOROS O2K). MEASUREMENTS AND MAIN RESULTS: The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 29 years old, respectively. In the Sepsis group, the median 1st 24-h SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared with 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared with the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared with the other group. There were no age-related differences in respiration between the Older and Younger control group. CONCLUSIONS: Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.
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